ABSTRACT The Animal Imaging Core provides individual projects with non-invasive, high-resolution quantitative imaging- based capabilities for metabolic, phenotypic, and genetic characterization of tumors and their microenvironment, including in vivo trafficking of tumor cells for rodent models of human cancer. This is accomplished by monitoring of ?directly-targeting? probes and of the expression of single-and multi-modality reporter genes using optical (bioluminescence and fluorescence), radionuclide (PET, SPECT, and autoradiography), MRI/MRS, CT, and US imaging. These non-invasive imaging techniques have long been established at MSK for small-animal imaging studies, are quantitative and thus readily adaptable to longitudinal studies. Co-localization of all animal imaging capabilites within the ZRC vivarium provides enhanced biosecurity and functionality and houses the Core?s Focus 120 microPET and Imveon microPET/microCT, Ivis Spectrum and Spectrum CT optical imaging systems NanoSPECT/CT Plu, and Vevo 2100 ultrasound system. The Ivis 100 optical imaging system has been upgraded to a Lumina II system and remains on the 12th floor of the Rockefeller Research Laboratory to provide ready access for investigators in that building. A new isocentric, image (CT)-guided microirradiator, the X-RAD 225Cx Image-Guided Biological Irradiator, for precise (down to 1-mm3) therapeutic irradiation of rodent tumors and other structures provides investigators with clinical-grade radiotherapy capability in terms of spatial accuracy and precision of dose delivery. The Core?s 7.0T 30-cm boreBruker NMR imaging and spectroscopy systems is within the ZRC Vivarium. The new PET insert (funded by RC2CA14897), which the Core recently received is compatible with the 7T magnet and is in current use. Additionally, the Core has an 11.7T vertical magnet and will shortly accept a new 9.4T magnet (funded by 1S10 OD023669) with an updated console (AV3) to replace the old 4.7T MR system) to be installed in this space as well. The Core also provides investigators with access to critical ancillary equipment and services such as a Fuji Film BAS-1800II phosphor-plate digital autoradiography system, a digital-camera- equipped Olympus B 201 fluorescence microscope with motorized stage, and a Microm HM500M cryostatic microtome and software such as SAAM II for linear and non-linear compartmental modeling, PMOD for voxel- based compartmental modeling/ parametric imaging, and OLINDA for internal radionuclide radiation dosimetry. The scientific value and cost-effectiveness of this state-of-the-art Animal Imaging Core is documented by the following (among other metrics): nearly 500 peer-reviewed Core-supported publications from 2013-2017 and 9 major instruments purchased with funding support provided by NIH and other Shared Instrumentation grants.